Differential prognostic impact of <scp><i>RUNX1</i></scp> mutations according to frontline therapy in patients with acute myeloid leukemia
Sangeetha Venugopal, Courtney D. DiNardo, Sanam Loghavi, Wei Qiao, Farhad Ravandi, Marina Konopleva, Tapan M. Kadia, Kapil N. Bhalla, Elias Jabbour, Ghayas C. Issa, Walid Macaron, Naval Daver, Gautam Borthakur, Guillermo Montalban‐Bravo, Musa Yılmaz, Keyur P. Patel, Rashmi Kanagal‐Shamanna, Kelly S. Chien, Abhishek Maiti, Hagop M. Kantarjian, Nicholas J. Short
Abstract
RUNX1-mutated (mRUNX1) acute myeloid leukemia (AML) has historically been associated with poor outcomes in the setting of conventional chemotherapy. The prognostic impact of mRUNX1 AML is not well-established in the current era of lower-intensity treatment regimens incorporating venetoclax. We retrospectively analyzed 907 patients with newly diagnosed AML, including 137 patients with mRUNX1 AML, who underwent first-line therapy with intensive chemotherapy (IC), low-intensity therapy without venetoclax (LIT without VEN), or LIT with VEN. When stratified by RUNX1 status, there was no statistically significant difference in outcomes between mRUNX1 and wild-type (wtRUNX1) AML, regardless of therapy received. However, among patients who received LIT with VEN, there was a trend towards superior overall survival (OS) in those with mRUNX1 AML (median OS for mRUNX1 vs. wtRUNX1: 25.1 vs. 11.3 months; 2-year OS 54% vs. 33%; p = 0.12). In patients without another adverse-risk cyto-molecular feature, the presence of mRUNX1 conferred inferior OS in patients who received IC (p = 0.02) or LIT without VEN (p = 0.003) but not in those who received LIT with VEN (mRUNX1 vs. wtRUNX1: 25.1 vs. 30.0 months; 2-year OS 59% vs. 54%; p = 0.86). A multivariate analysis showed possible interaction between RUNX1 mutation status and treatment, suggesting a differential prognostic impact of RUNX1 mutations when patients received IC versus LIT with VEN. In summary, the prognostic impact of mRUNX1 AML may be treatment-dependent, and the presence of RUNX1 mutations may not impact clinical outcomes when venetoclax-based regimens are used.